Following an insult to the cornea, the immune and inflammatory systems respond to protect the integrity of the eye. This protective mechanism can have clinical manifestations ranging from cellular infiltration to ulcer formation. Though protective, these processes often compromise the primary function of the eye by causing vascularization, scarring and/or perforation of the cornea.
For example, it has been demonstrated that exposure of the abraded corneal surface to lipopolysaccharide (LPS) or other bacterial products induces corneal inflammation causing neutrophil-rich infiltrates in the corneal stroma (Johnson et al., Invest. Ophthalmol Vis. Sci. 2005; 46:589-595; Khatri et al., Invest. Opthalmol. Vis. Sci. 2002; 43:2278-2284; Schultz et al., Infection and Immunity 2000; 68:1731-1734; Schultz et al., Exper. Eye Res. 1997; 64:3-9; Sun et al., Infection and Immunity 2006; 74:5325-5332).
When there is an insult to the corneal surface, inflammatory and/or immune cells are sent to repair the damage. These cells can aggregate in a region of the cornea and are visible as clinically identifiable infiltrates. This infiltrate formation and resultant corneal inflammation can arise from either infectious or non-infectious conditions. One infectious condition that can adversely affect the cornea is bacterial keratitis. Major causes of bacterial keratitis in the USA and worldwide include infection by Pseudomonas aeruginosa, Staphylococcus aureus, S. epidermidis and Streptococcus species. In developing countries, bacterial keratitis is primarily associated with trauma related to agricultural work; whereas, in industrialized countries, bacterial keratitis is associated with contact lens wear.
In addition to infectious keratitis, contact lens wear is also associated with sterile, culture-negative clinical manifestations, including contact lens associated red eye (CLARE), contact lens peripheral ulcers (CLPU), and contact lens associated corneal infiltrates CLACI (Stapleton et al., Optom Vis Sci. 2007; 84:257-272). Although symptoms from these manifestations are less severe than symptoms associated with infectious keratitis, affected individuals have pain, redness, blurred vision and severe discomfort. Given that the number of contact lens wearers exceeds 34 million in the USA and 140 million worldwide, the relatively small percentage of contact lens wearers with these clinical manifestations translates to large total number of individuals affected (Stapleton et al., Optom. Vis. Sci. 2007; 84:257-272).
Currently, steroid use is the only treatment for corneal infiltrates. The side effects of steroid use are considerable. In infectious keratitis, steroids are given only after resolution of infection; otherwise, they can have an adverse effect on the infection. Furthermore, steroid use can cause increased ocular pressure, thereby increasing the risk of glaucoma, and are often administered together with anti-glaucoma treatment.